全文获取类型
收费全文 | 2014篇 |
免费 | 179篇 |
国内免费 | 2篇 |
专业分类
2195篇 |
出版年
2023年 | 14篇 |
2022年 | 28篇 |
2021年 | 58篇 |
2020年 | 25篇 |
2019年 | 29篇 |
2018年 | 47篇 |
2017年 | 32篇 |
2016年 | 70篇 |
2015年 | 107篇 |
2014年 | 95篇 |
2013年 | 126篇 |
2012年 | 181篇 |
2011年 | 166篇 |
2010年 | 113篇 |
2009年 | 85篇 |
2008年 | 126篇 |
2007年 | 130篇 |
2006年 | 133篇 |
2005年 | 97篇 |
2004年 | 99篇 |
2003年 | 86篇 |
2002年 | 80篇 |
2001年 | 24篇 |
2000年 | 22篇 |
1999年 | 22篇 |
1998年 | 19篇 |
1997年 | 6篇 |
1996年 | 11篇 |
1995年 | 9篇 |
1994年 | 15篇 |
1993年 | 11篇 |
1992年 | 11篇 |
1991年 | 9篇 |
1990年 | 14篇 |
1989年 | 9篇 |
1988年 | 9篇 |
1987年 | 6篇 |
1986年 | 5篇 |
1985年 | 6篇 |
1984年 | 3篇 |
1983年 | 6篇 |
1982年 | 4篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1978年 | 11篇 |
1975年 | 5篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1967年 | 3篇 |
1966年 | 2篇 |
排序方式: 共有2195条查询结果,搜索用时 0 毫秒
81.
82.
Michelle L Cloutier A Toutant J Shkreta L Thibault P Durand M Garneau D Gendron D Lapointe E Couture S Le Hir H Klinck R Elela SA Prinos P Chabot B 《Molecular and cellular biology》2012,32(5):954-967
Several apoptotic regulators, including Bcl-x, are alternatively spliced to produce isoforms with opposite functions. We have used an RNA interference strategy to map the regulatory landscape controlling the expression of the Bcl-x splice variants in human cells. Depleting proteins known as core (Y14 and eIF4A3) or auxiliary (RNPS1, Acinus, and SAP18) components of the exon junction complex (EJC) improved the production of the proapoptotic Bcl-x(S) splice variant. This effect was not seen when we depleted EJC proteins that typically participate in mRNA export (UAP56, Aly/Ref, and TAP) or that associate with the EJC to enforce nonsense-mediated RNA decay (MNL51, Upf1, Upf2, and Upf3b). Core and auxiliary EJC components modulated Bcl-x splicing through different cis-acting elements, further suggesting that this activity is distinct from the established EJC function. In support of a direct role in splicing control, recombinant eIF4A3, Y14, and Magoh proteins associated preferentially with the endogenous Bcl-x pre-mRNA, interacted with a model Bcl-x pre-mRNA in early splicing complexes, and specifically shifted Bcl-x alternative splicing in nuclear extracts. Finally, the depletion of Y14, eIF4A3, RNPS1, SAP18, and Acinus also encouraged the production of other proapoptotic splice variants, suggesting that EJC-associated components are important regulators of apoptosis acting at the alternative splicing level. 相似文献
83.
84.
Variations in aspartasic activity in various media are due to aspartate-ammonium lyase induction and to regulation of the biosynthesis of this enzyme. Evidence for neosynthesis of the enzyme is provided by labelling and separation of the protein. The inducer appears to be aspartic acid. The biosynthesis is subject to pronounced catabolic repression. The physiological function of aspartate-ammonium lyase is discussed. 相似文献
85.
Didier Menard Ernest R. Chan Christophe Benedet Arsène Ratsimbasoa Saorin Kim Pheaktra Chim Catherine Do Benoit Witkowski Remy Durand Marc Thellier Carlo Severini Eric Legrand Lise Musset Bakri Y. M. Nour Odile Mercereau-Puijalon David Serre Peter A. Zimmerman 《PLoS neglected tropical diseases》2013,7(11)
Background
Plasmodium vivax is the most prevalent human malaria parasite, causing serious public health problems in malaria-endemic countries. Until recently the Duffy-negative blood group phenotype was considered to confer resistance to vivax malaria for most African ethnicities. We and others have reported that P. vivax strains in African countries from Madagascar to Mauritania display capacity to cause clinical vivax malaria in Duffy-negative people. New insights must now explain Duffy-independent P. vivax invasion of human erythrocytes.Methods/Principal Findings
Through recent whole genome sequencing we obtained ≥70× coverage of the P. vivax genome from five field-isolates, resulting in ≥93% of the Sal I reference sequenced at coverage greater than 20×. Combined with sequences from one additional Malagasy field isolate and from five monkey-adapted strains, we describe here identification of DNA sequence rearrangements in the P. vivax genome, including discovery of a duplication of the P. vivax Duffy binding protein (PvDBP) gene. A survey of Malagasy patients infected with P. vivax showed that the PvDBP duplication was present in numerous locations in Madagascar and found in over 50% of infected patients evaluated. Extended geographic surveys showed that the PvDBP duplication was detected frequently in vivax patients living in East Africa and in some residents of non-African P. vivax-endemic countries. Additionally, the PvDBP duplication was observed in travelers seeking treatment of vivax malaria upon returning home. PvDBP duplication prevalence was highest in west-central Madagascar sites where the highest frequencies of P. vivax-infected, Duffy-negative people were reported.Conclusions/Significance
The highly conserved nature of the sequence involved in the PvDBP duplication suggests that it has occurred in a recent evolutionary time frame. These data suggest that PvDBP, a merozoite surface protein involved in red cell adhesion is rapidly evolving, possibly in response to constraints imposed by erythrocyte Duffy negativity in some human populations. 相似文献86.
Assessing the impacts of imperfect detection on estimates of diversity and community structure through multispecies occupancy modeling 下载免费PDF全文
Detecting all species in a given survey is challenging, regardless of sampling effort. This issue, more commonly known as imperfect detection, can have negative impacts on data quality and interpretation, most notably leading to false absences for rare or difficult‐to‐detect species. It is important that this issue be addressed, as estimates of species richness are critical to many areas of ecological research and management. In this study, we set out to determine the impacts of imperfect detection, and decisions about thresholds for inclusion in occupancy, on estimates of species richness and community structure. We collected data from a stream fish assemblage in Algonquin Provincial Park to be used as a representation of ecological communities. We then used multispecies occupancy modeling to estimate species‐specific occurrence probabilities while accounting for imperfect detection, thus creating a more informed dataset. This dataset was then compared to the original to see where differences occurred. In our analyses, we demonstrated that imperfect detection can lead to large changes in estimates of species richness at the site level and summarized differences in the community structure and sampling locations, represented through correspondence analyses. 相似文献
87.
Christina C. Roggatz Mark Lorch Jrg D. Hardege David M. Benoit 《Global Change Biology》2016,22(12):3914-3926
Ocean acidification is a global challenge that faces marine organisms in the near future with a predicted rapid drop in pH of up to 0.4 units by the end of this century. Effects of the change in ocean carbon chemistry and pH on the development, growth and fitness of marine animals are well documented. Recent evidence also suggests that a range of chemically mediated behaviours and interactions in marine fish and invertebrates will be affected. Marine animals use chemical cues, for example, to detect predators, for settlement, homing and reproduction. But, while effects of high CO2 conditions on these behaviours are described across many species, little is known about the underlying mechanisms, particularly in invertebrates. Here, we investigate the direct influence of future oceanic pH conditions on the structure and function of three peptide signalling molecules with an interdisciplinary combination of methods. NMR spectroscopy and quantum chemical calculations were used to assess the direct molecular influence of pH on the peptide cues, and we tested the functionality of the cues in different pH conditions using behavioural bioassays with shore crabs (Carcinus maenas) as a model system. We found that peptide signalling cues are susceptible to protonation in future pH conditions, which will alter their overall charge. We also show that structure and electrostatic properties important for receptor binding differ significantly between the peptide forms present today and the protonated signalling peptides likely to be dominating in future oceans. The bioassays suggest an impaired functionality of the signalling peptides at low pH. Physiological changes due to high CO2 conditions were found to play a less significant role in influencing the investigated behaviour. From our results, we conclude that the change of charge, structure and consequently function of signalling molecules presents one possible mechanism to explain altered behaviour under future oceanic pH conditions. 相似文献
88.
Indirect evidence that agricultural pesticides select for insecticide resistance in the malaria vector Anopheles gambiae 下载免费PDF全文
Djogbénou S. Luc Assogba Benoit Djossou Laurette Makoutode Michel 《Journal of vector ecology》2016,41(1):34-40
We investigated the possible relationship between the agricultural use of insecticides and the emergence of insecticide resistance. Bioassays were conducted using simulated mosquito larval habitats and well known Anopheles gambiae strains. Soil samples were collected from vegetable production areas in Benin, including one site with insecticide use, one site where insecticides had not been used for two months, and a third where insecticides had not been used. Pupation and emergence rates were very low in pyrethroid‐susceptible strains when exposed to soil that had been recently exposed to insecticides. Pupation and emergence rates in strains with the kdr mutation alone or both the kdr and Ace‐1 mutations were much higher. Overall, strains with the kdr mutation survived at higher rates compared to that without kdr mutation. Although this study is observational, we provide indirect evidence indicating that soils from agricultural areas contain insecticide residues that can play a role in the emergence of insecticide resistance in Anopheles. This aspect should be taken into account to better utilize the insecticide in the context of integrated pest management programs. 相似文献
89.
Dermal glands (sensilla sagittiformia) secrete when brown dog ticks, Rhipicephalus sanguineus, are mechanically disturbed, presumably as a defensive mechanism. Recently, we observed that these glands secrete due to the pressure stimulation of engorgement. In this study, we examine how dermal gland secretion alters the physiology of R. sanguineus, particularly if this secretion is an important mechanism during blood feeding. The ability of ticks to retain water was not modified by dermal gland secretion, but heat tolerance was enhanced. Short-term heat shock was improved slightly (1 h at 50 °C to 1 h at 56 °C) and featured reduced injury responses and greater recovery after heat shock. When exposed to their host body temperature (37 °C) for prolonged periods, individuals that had secreted survived over 1 week longer than individuals that did not secrete. Dorsal application of squalene, the main component of dermal gland secretion, did not increase temperature tolerance, suggesting that the act of secreting rather than the physical properties of the secretion itself is responsible for the increase in heat tolerance. Based on our results, dermal gland secretion may be an essential mechanism in certain tick species (Amblyomma, Dermacentor, Hyalomma, Rhipicephalus, but not Ixodes) for tolerating body temperature and not succumbing to heat stress during the extended time periods of feeding on a mammalian host, serving as a mechanism to prevent heat damage from the host during feeding. 相似文献
90.
Coïc YM Baleux F Poyraz Ö Thibeaux R Labruyere E Chretien F Sobhani I Lazure T Wyplosz B Schneider G Mulard L Sansonetti PJ Marteyn BS 《The Journal of biological chemistry》2012,287(19):15916-15922
Imaging living cells and organs requires innovative, specific, efficient, and well tolerated fluorescent markers targeting cellular components. Such tools will allow proceeding to the dynamic analysis of cells and the adaptation of tissues to environmental cues. In this study, we have identified and synthesized a novel non-toxic fluorescent marker allowing a specific fluorescent staining of the human colonic mucus. Our strategy to identify a molecule able to specifically bind to the human colonic mucus was on the basis of the mucus adhesion properties of commensal bacteria. We identified and characterized the mucus-binding property of a 70-amino acid domain (MUB(70)) expressed on the surface of Lactobacillus strains. The chemical synthesis of MUB(70) was achieved using the human commensal bacterium Lactobacillus reuteri AF120104 protein as a template. The synthesized Cy5-conjugated MUB(70) marker specifically stained the colonic mucus on fixed human, rabbit, and guinea pig tissues. Interestingly, murine tissue was not stained, suggesting significant differences in the composition of the murine colonic mucus. In addition, this marker stained the mucus of living cultured human colonic cells (HT29-MTX) and human colonic tissue explants. Using a biotinylated derivative of MUB(70), we demonstrated that this peptide binds specifically to Muc2, the most abundant secreted mucin, through its glycosylated moieties. Hence, Cy5-MUB(70) is a novel and specific fluorescent marker for mammalian colonic mucus. It may be used for live imaging analysis but also, as demonstrated in this study, as a marker for the diagnosis and the prognosis of colonic mucinous carcinomas. 相似文献